Viral Dynamics and Pharmacokinetics of Abacavir and Tenofovir

Summary

Once-daily nucleotide/nucleoside reverse transcriptase inhibitor (NtRTI/NRTI) combinations form the backbone of many regimens. Although efficacy data exists between tenofovir and the pyrimidine analogues (i.e. lamivudine and emtricitabine), recent clinical data suggests a potential interaction between tenofovir and purine analogs (i.e. abacavir and didanosine). Specific Aim 1: To evaluate the impact of an acyclic nucleoside phosphonate, tenofovir (TDF), on the intracellular metabolism of a purine nucleoside analog, abacavir (ABC), as a determinant of the antiviral potency of this nucleotide/nucleoside reverse transcriptase inhibitor (NtRTI/NRTI) combination. * Hypothesis #1: ABC and TDF dosed together will have reduced antiviral activity, as measured by early plasma HIV RNA decay kinetics, than the drugs given alone. * Hypothesis #2: ABC dosed with TDF will have reduced intracellular concentrations, as measured by the ratio of carbovir triphosphate (active metabolite of ABC) to deoxyguanosine triphosphate (endogenous nucleotide), compared to ABC given alone.

Timeline

Start

2004-12-07

Primary completion

2008-06-26

Completion

2010-04-27

Publications

• Results Goicoechea M, Jain S, Bi L, Kemper C, Daar ES, Diamond C, Ha B, Flaherty J, Sun S, Richman D, Louie S, Haubrich R; California Collaborative Treatment Group. Abacavir and tenofovir disoproxil fumarate co-administration results in a nonadditive antiviral effect in HIV-1-infected patients. AIDS. 2010 Mar 13;24(5):707-16. doi: 10.1097/QAD.0b013e32833676eb.

Drugs

Indications